P889: POINT-OF-CARE ANTI-BCMA CAR T-CELL THERAPY INDUCES ENCOURAGING RESPONSE RATES IN HIGH-RISK RELAPSE/REFRACTORY MULTIPLE MYELOMA
Authors: Hila Magen, Shalev Fried, Orit Itzhaki, Noga Shem-Tov, Ivetta Danylesko, Ronit Yerushalmi, Roni Shouval, Ronit Marcus, Lee Nevo, Ronnie Shapira-Frommer, Arnon Nagler, Avichai Shimoni, Eden Shkury, Avigdor Abraham
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Anti-BCMA chimeric antigen receptor (CAR) T-cell therapy showed excellent efficacy and safety in patients with relapsed/refractory multiple myeloma (R/R MM). Point-of-care (POC) CAR manufacturing abrogates the need for cryopreservation and shipment of cells, thus shortening the manufacturing process and reducing the necessity of bridging therapy. Aims: To report outcomes of phase 1b/2 single-center clinical trial of autologous POC anti-BCMA CAR T-cell therapy in patients (pts) with R/R MM treated with ≥3 prior therapies (NCT05243212). Methods: R/R MM pts underwent a single peripheral blood leukapheresis. Fresh T-cells were isolated, activated, and transduced with retroviral vector encoding the anti-BCMA CAR (based on 11D5-3 ScFv, CD28 costimulatory domain, and CD3-ζ signaling domain). Lymphodepletion conditioning included fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 over 3 days (days −4 to −2) followed by infusion of 6×106/kg (dose level I [n=3]) or 9×106/kg (dose level II [n=29]) CAR T-cells in the inpatient setting. Primary endpoints were overall response rate per International Myeloma Working Group criteria and safety. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). Last follow-up was as of 02/2023. Results: All 32 pts (median age 60, IQR 54-67) enrolled received CAR T-cell infusion in a median of 11 days (IQR 11-11) after leukapheresis. Only 2 pts received bridging chemotherapy. The median number of prior therapies was 4 (IQR 3-5), with 59% and 34% of the pts being penta- and quad-refractory, respectively. All pts were proteasome inhibitors and IMiD-agent refractory, 31 (97%) were daratumumab refractory, and 7 (22%) pts had prior exposure to BCMA-targeted therapy (belantamab mafodotin, n=5 [16%]; talqeutamab, n=2 [6%]). At enrollment, 10 (34%) pts had high-risk cytogenetics, 7 (22%) had double-hit myeloma, 11 (37%) had bone-marrow plasma cell percentage ≥50%, and 17 (57%) had extramedullary involvement. Only 17 (53%) and 2 (16%) pts were eligible to enroll in the KarMMa (NEJM, 2021) and CARTITUDE-1 (Lancet, 2021) studies, respectively. CAR T-cell therapy was well tolerated in all pts. Only 1 patient (3%) developed grade 3 cytokine release syndrome. Immune effector cell-associated neurotoxicity syndrome was not noted. Grade 3-4 neutropenia and thrombocytopenia occurred in 31 (97%) and 16 (50%), respectively. Anemia requiring transfusion occurred in 14 (44%) pts. Grade 3-4 neutropenia, thrombocytopenia and anemia beyond day 60 were present in 3 (9%), 11 (34%), and 12 (38%) pts, respectively. No bleeding events nor cellular therapy-related deaths were observed. The median follow-up was 3.9 months (IQR 2.6-7.3). Best Overall response rate (PR at least) was 59% (VGPR at least, 40%). Median time to first response was 31 days (95% CI: 26-33). Estimated 6-months OS, PFS and duration of response were 89% (95% CI: 75-100), 48% (95% CI: 33-72), and 63% (95% CI: 41-97), respectively. Patients with prior exposure to BCMA-targeted therapies had an inferior PFS (HR 3.4 [95% CI: 1.2-9.7] p=0.03; Figure 1). Summary/Conclusion: POC anti-BCMA CAR T-cells induced high response rates with an excellent safety profile in high-risk MM patients mosly not eligible to be enrolled in the pivotal trials. The rapid CAR-T production time obviated the need for bridging therapy in most patients. It is noteworthy that prior exposure to BCMA-targeted therapies is associated with dismal PFS, hence those therapies should be carefully considered when CAR T-cell therapy might be intended. * The first and last two authors contributed equally to the abstract.Keywords: Clinical trial, Point-of-care, CAR-T, Multiple myeloma